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Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene

Miller, Shyra J., Jessen, Walter J., Mehta, Tapan, Hardiman, Atira, Sites, Emily, Kaiser, Sergio, Jegga, Anil G., Li, Hua, Upadhyaya, Meena, Giovannini, Marco, Muir, David, Wallace, Margaret R., Lopez, Eva, Serra, Eduard, Nielsen, G. Petur, Lazaro, Conxi, Stemmer-Rachamimov, Anat, Page, Grier, Aronow, Bruce J. and Ratner, Nancy 2009. Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Molecular Medicine 1 (4) , pp. 236-248. 10.1002/emmm.200900027

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Understanding the biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour biomarkers, prognostic factors and therapeutics. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n=10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n=22), malignant peripheral nerve sheath tumour (MPNST) cell lines (n=13), benign neurofibromas (NF) (n=6) and MPNST (n=). Dermal and plexiform NFs were indistinguishable. A prominent theme in the analysis was aberrant differentiation. NFs repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes up-regulated in sarcomas were significantly enriched for genes activated in neural crest cells. We validated the differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting SOX9 – strongly expressed in NF1-related tumours – caused MPNST cell death. SOX9 is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: MPNST; neurofibroma; NF1; Schwann cell; Sox9
Publisher: John Wiley & Sons
ISSN: 1757-4676
Last Modified: 04 Jun 2017 03:32

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